Disease-modifying drugs in osteoarthritis: current understanding and future therapeutics

Oo, Win Min; Yu, Shirley P.; Daniel, Matthew; Hunter, David J.

doi:10.1080/14728214.2018.1547706

Cited by 142 publications

(116 citation statements)

References 151 publications

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“…OA is a leading cause of pain and disability among adults with a current prevalence of around 15% and a predicted prevalence of 35% in 2030 for symptomatic OA. 6 With an aging population, these numbers will only continue to rise. Symptomatic and advanced knee OA is particularly impactful on overall health and mobility.…”

Section: Discussionmentioning

confidence: 99%

Micronized Dehydrated Human Amnion Chorion Membrane Injection in the Treatment of Knee Osteoarthritis—A Large Retrospective Case Series

et al. 2019

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Osteoarthritis (OA) of the knee is a leading cause of chronic pain and disability in the United States. Current treatment options primarily target OA symptoms reserving surgical intervention and knee replacement for those who fail conservative measures. With average age of patients with knee OA decreasing, regenerative treatment approaches to reduce symptoms, increase quality of life, and delay the need for surgical intervention are increasingly sought. Human amniotic membrane contains growth factors and cytokines, which promote epithelial cell migration and proliferation, stimulate metabolic processes leading to collagen synthesis, and attract fibroblasts, while also reducing pain and inflammation. Micronization of the tissue allows for suspension in normal saline and injection. We conducted a retrospective review of 100 knees treated for symptomatic OA with micronized dehydrated human amnion/chorion membrane (mdHACM) and followed for 6 months. Our purpose is to present our experience and patient outcomes. Data were abstracted from electronic medical records of 82 consecutive OA patients (100 knees) injected with 100 mg mdHACM. Patient age, gender, adverse events and routinely collected Knee Injury and Osteoarthritis Outcome Score (KOOS) were evaluated. Effectiveness of mdHACM treatment was measured by serial KOOS at baseline, and posttreatment at 6 weeks, 3, and 6 months. Overall mean KOOS for the cohort was 40 at baseline, improving to 52, 62, and 65 at 6 weeks, 3 months, and 6 months post-mdHACM injection. Percent increases were 32, 56, and 65%, respectively. Quality of life and sports/recreation domains improved by 111 and 118%, respectively, at 6 months. Pain scores improved by 67% at 6 months. All scores improved throughout the observation period. The most common adverse event was pain after injection lasting 2 to 7 days, observed in 68% of cases. This represents the largest single-physician experience with mdHACM for treatment of knee OA reported to date. Injectable mdHACM appears to be a potentially useful treatment option for knee OA patients. Controlled studies are underway to confirm these observations.

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Section: Discussionmentioning

confidence: 99%

Micronized Dehydrated Human Amnion Chorion Membrane Injection in the Treatment of Knee Osteoarthritis—A Large Retrospective Case Series

et al. 2019

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“…Reasons for failure of DMOAD trials in recent years are complex but include X-ray based eligibility screening 6,14,16 . X-ray is only able to depict osseous changes and is not able to show OA-related tissue changes other than osteophytes, joint space narrowing, sclerosis, cysts and attrition -features that are commonly not considered treatment targets.…”

Section: Discussionmentioning

confidence: 99%

MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES)

Roemer

Collins

Kwoh

et al. 2020

Osteoarthritis and Cartilage

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Purpose: Our aim was to introduce a simplified MRI instrument, Rapid OsteoArthritis MRI Eligibility Score (ROAMES), for defining structural eligibility of patients for inclusion in disease-modifying osteoarthritis drug trials using a tri-compartmental anatomic approach that enables stratification of knees into different structural phenotypes and includes diagnoses of exclusion. We also aimed to define overlap between phenotypes and determine reliability. Methods: 50 knees from the Foundation for National Institutes of Health Osteoarthritis Biomarkers study, a nested case-control study within the Osteoarthritis Initiative, were selected within pre-defined definitions of phenotypes as either inflammatory, subchondral bone, meniscus/cartilage, atrophic or hypertrophic. A focused scoring instrument was developed covering cartilage, meniscal damage, inflammation and osteophytes. Diagnoses of exclusion were meniscal root tears, osteonecrosis, subchondral insufficiency fracture, tumors, malignant marrow infiltration and acute traumatic changes. Reliability was determined using weighted kappa statistics. Descriptive statistics were used for determining concordance between the a priori phenotypic definition and ROAMES and overlap between phenotypes. Results: ROAMES identified 43 of 50 (86%) pre-defined phenotypes correctly. Of the 50 participants, 27 (54%) had no additional phenotypes other than the pre-defined phenotype. 18 (36%) had one and 5 (10%) had two additional phenotypes. None had three or four additional phenotypes. All features of ROAMES showed almost perfect agreement. One case with osteonecrosis and one with a tumor were detected. Conclusions: ROAMES is able to screen and stratify potentially eligible knees into different structural phenotypes and record relevant diagnoses of exclusion. Reliability of the instrument showed almost perfect agreement.

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“…OA is a complex disease associated with inflammatory, however, approved drugs that can prevent, slow or reverse the progression of OA are still limited. 1 SHM was one of classic TCM with significant anti-inflammatory and analgesic effects on acute soft tissue injury. 15 Our study identified 16 key active ingredients of SHM, of which quercetin were validated through TLC.…”

Section: Discussionmentioning

confidence: 99%

“…Osteoarthritis (OA) is one of the most common cause of pain and disability among the elderly and adults of working age around the world with a current prevalence of approximately 15% and a predicted prevalence of 35% in 2030. 1,2 OA has long been considered as a "wear and tear" disease, characterized by losing articular cartilage and subchondral bone sclerosis. Today it has been generally accepted that inflammation-driven by innate immunological mechanisms plays a key role in tissue destruction in OA.…”

Section: Introductionmentioning

confidence: 99%

<p>Validation of the Key Active Ingredients and Anti-Inflammatory and Analgesic Effects of Shenjin Huoxue Mixture Against Osteoarthritis by Integrating Network Pharmacology Approach and Thin-Layer Chromatography Analysis</p>

Yu¹,

Ma²,

Song³

et al. 2020

DDDT

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Background: Shenjin Huoxue Mixture (SHM), a classic traditional herb mixture has shown significant clinical efficacy against osteoarthritis (OA). Our previous experimental study has confirmed its anti-inflammatory and analgesic effect on acute soft tissue injury in rats, with the compound of glycyrrhizinate in SHM identified and the content of paeoniflorin in SHM determined by high-performance liquid chromatography (HPLC). However, the components and its pharmacological mechanisms of SHM against OA have not been systematically elucidated yet. Thus this study aimed to predict the key active ingredients and potential pharmacological mechanisms of SHM in the treatment of OA by network pharmacology approach and thin-layer chromatography (TLC) validation. Methods: The active ingredients of SHM and their targets, as well as OA-related targets, were identified from databases. The key active ingredients were defined and ranked by the number of articles retrieved in PubMed using the keyword "(the active ingredients [Title/Abstract]) AND Osteoarthritis[Title/Abstract] ", and validated partially by TLC. The pharmacological mechanisms of SHM against OA were displayed by GO term and Reactome pathway enrichment analysis with Discovery Studio 3.0 software docking to testing the reliability. Results: Finally, 16 key active ingredients were identified and ranked, including quercetin validated through TLC. Inflammatory response, IL-6 signaling pathway and toll-like receptor (TLR) cascades pathway were predicted as the main pharmacological mechanisms of SHM against OA. Especially, 12 out of 16 key active ingredients, including validated quercetin, were well docked to IL-6 proteins. Conclusion: Our results confirmed the anti-inflammatory and analgesic effect of SHM against OA through multiple components, multiple targets and multiple pathways, which revealed the theoretical basis of SHM against OA and may provide a new drug option for treating OA.

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Disease-modifying drugs in osteoarthritis: current understanding and future therapeutics

Cited by 142 publications

References 151 publications

Micronized Dehydrated Human Amnion Chorion Membrane Injection in the Treatment of Knee Osteoarthritis—A Large Retrospective Case Series

Micronized Dehydrated Human Amnion Chorion Membrane Injection in the Treatment of Knee Osteoarthritis—A Large Retrospective Case Series

MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES)

<p>Validation of the Key Active Ingredients and Anti-Inflammatory and Analgesic Effects of Shenjin Huoxue Mixture Against Osteoarthritis by Integrating Network Pharmacology Approach and Thin-Layer Chromatography Analysis</p>

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